comparative trial of pivanex and docetaxel vs docetaxel monotherapy in patients with advanced non-small cell lung cancer

Conditions: Carcinoma, Non-Small-Cell Lung

Summary: this randomized study will assess the efficacy and safety of the combination of pivanex and docetaxel compared to docetaxel alone in patients with a type of lung cancer called non-small cell lung cancer. pivanex is an investigational agent, and docetaxel is an approved drug.

rationale: pivanex is a histone deacetylase inhibitor that induces tumor differentiation and/or apoptosis. pivanex has been well tolerated in clinical trials and has shown preliminary evidence of efficacy in patients with non-small cell lung cancer. docetaxel is an approved drug for second-line treatment of non-small cell lung cancer. preclinical studies indicate that the combination of pivanex and docetaxel is synergistic. purpose: this open-label randomized trial will evaluate whether combination therapy with pivanex and docetaxel provides clinical benefit over docetaxel alone in patients with chemotherapy resistant non-small cell lung cancer. objectives: * compare the survival of patients with non-small cell lung cancer treated with combination therapy with pivanex and docetaxel vs. docetaxel alone * compare the time to disease progression, tumor responses, and safety profile of patients with non-small cell lung cancer treated with combination therapy with pivanex and docetaxel vs. docetaxel alone outline: this is a randomized, open-label, multicenter study in patients with non-small cell lung cancer who have previously been treated with no more than one prior platinum containing chemotherapy regimen. patients are stratified by ecog performance status (0-1 vs. 2), response to prior platinum based chemotherapy (progression vs. cr/pr/sd) and prior taxane therapy (yes vs. no). patients are randomized to 1 of 2 treatment arms. * arm a: patients receive the combination of pivanex intravenously on days 1-3 and docetaxel intravenously on day 4. treatment repeats every 21 days until disease progression or treatment withdrawal. * arm b: patients receive docetaxel intravenously on day 1. treatment repeats every 21 days until disease progression or treatment withdrawal.

Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed non-small cell lung cancer (nsclc); treatment with one prior platinum-based chemotherapy regimen (eligible patients may include: 1. patients previously treated with adjuvant or neoadjuvant chemotherapy (must be completed within 6 months prior to randomization) or 2. patients who have received chemotherapy for advanced or metastatic lung cancer); * recurrent or progressive nsclc (local, distant, or both) following initial chemotherapy); * measurable or non-measurable disease; * males and females, age =\> 18 years; * adequate renal function with creatinine =\> 1.5 mg/dl; * adequate liver function with alkaline phosphatase =\> 2.5 x upper limit of normal, sgot, and sgpt =\> 1.5 x upper limit of normal; and total bilirubin =\> upper limit of normal; * adequate bone marrow function: platelets \> 100,000/mm3, hemoglobin =\> 9 g/dl, and absolute neutrophil count (anc) =\> 1,500 cells/mm3; * able to give informed consent; * discontinuation of previous surgery, radiation therapy or cancer chemotherapy at least four weeks prior to randomization (six weeks if a prior nitrosourea or mitomycin c), with recovery from treatment-associated toxicity; * a predicted life expectancy of at least 12 weeks; and * ecog performance status of 0, 1, or 2. exclusion criteria: * receipt of more than one chemotherapy regimen for nsclc; * a second malignancy within the last 5 years other than curatively treated carcinoma-in-situ or non-melanoma skin cancer; * pregnant or lactating females (females of childbearing potential must have a negative pregnancy test and all male and female patients of reproductive potential must agree to use adequate birth control); * known hiv-positive patients; * acute medical problems, such as ischemic heart or lung disease or uncontrolled systemic infection; * patients with any underlying medical conditions or circumstance, which would contraindicate therapy with study treatment, affect compliance or impair evaluation of study endpoints; * patients receiving investigational agents within 30 days of the screening visit; * known allergy to reagents in the study; * prior docetaxel therapy; * symptomatic or untreated brain metastases (patients with brain metastases are eligible if they are clinically and neurologically stable for \> 4 weeks since therapy (radiation therapy, radiosurgery/gamma knife; surgical resection) as determined by the investigator and either off corticosteroids or on a stable dose of corticosteroids).

Keywords: lung cancer, docetaxel, histone deacetylase inhibitor